Undercarboxylated osteocalcin as a biomarker of subclinical atherosclerosis in non-dialysis patients with chronic kidney disease

Background

Studies in recent years have shown that undercarboxylated osteocalcin (uOC) not only maintains bone mineralization, but is also involved in the regulation of atherosclerosis. However, a correlation between uOC and carotid atherosclerosis in non-dialysis patients with chronic kidney disease (CKD) has not been investigated.A total of 240 non-dialysis patients with CKD were included in the study. For these patients, the median estimated glomerular filtration rate (eGFR) was 20.05 (12.43–49.32) ml/min/1.73m². Serum uOC levels were measured using enzyme-linked immunosorbent assay (ELISA). Carotid ultrasonography was performed to assess carotid atherosclerotic plaques and intima–media thickness (IMT) in an attempt to analyze the relationship between uOC level and carotid atherosclerosis.

Results

The uOC levels of non-dialysis patients with CKD were significantly lower than those of healthy controls [28.16 (21.40–45.85) ng/mL vs. 36.42 (28.05–49.28) ng/mL, P < 0.01]. The uOC levels gradually decreased as CKD progressed (P < 0.01). The uOC levels were significantly lower in patients with carotid plaques than in patients without carotid plaques [25.98 (20.14–31.35) ng/mL vs. 31.02 (25.86–36.40) ng/mL, P < 0.01]. uOC level showed significant negative correlation with IMT (r = -0.33, P < 0.01). Logistic regression analysis revealed that after adjustment for various confounding factors, decreased uOC levels were shown to indicate increased possibility of carotid atherosclerotic plaque development in non-dialysis patients with CKD (on every 1 SD decrease in the uOC level, odds ratio 1.70, 95 % confidence interval 1.24–2.98, P < 0.01). Multivariate stepwise regression analysis demonstrated that decreased uOC level (β = -0.163, P < 0.05) was an independent risk factor for increased carotid IMT in non-dialysis patients with CKD.

Conclusion

Serum uOC levels in non-dialysis patients with CKD are significantly lower than those in healthy individuals, and uOC is closely associated with subclinical atherosclerosis in CKD patients.     

Niacin improves renal lipid metabolism and slows progression in chronic kidney disease

Background

Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF.

Methods

Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats.

Results

CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-α, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-α and L-FABP.

Conclusions and general significance

Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.     

Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease

ABSTRACT

Uric acid (UA) is a potential risk factor of the progression of chronic kidney disease (CKD). Recently, we reported that intestinal UA excretion might be enhanced via upregulation of the ATP-binding cassette transporter G2 (Abcg2) in a 5/6 nephrectomy (Nx) rat model. In the present study, we examined the mRNA and protein expressions of UA transporters, URAT1, GLUT9/URATv1, ABCG2 and NPT4 in the kidney and ileum in the same rat model. Additionally, we investigated the Abcg2 mRNA expression of ileum in hyperuricemic rat model by orally administering oxonic acid. Male Wistar rats were randomly assigned to three groups consisting of Nx group, oxonic acid-treated (Ox) group and sham-operated control group, and sacrificed at 8 weeks. Creatinine and UA were measured and the mRNA expressions of UA transporters in the kidney and intestine were evaluated by a real time PCR. UA transporters in the kidney sections were also examined by immunohistochemistry. Serum creatinine elevated in the Nx group whereas serum UA increased in the Ox group. Both the mRNA expression and the immunohistochemistry of the UA transporters were decreased in the Nx group, suggesting a marginal role in UA elevation in decreased kidney function. In contrast, the mRNA expression of Abcg2 in the ileum significantly increased in the Ox group. These results suggest that the upregulation of Abcg2 mRNA in the ileum triggered by an elevation of serum UA may play a compensatory role in increasing intestinal UA excretion.     

DIBc nano metal-organic framework improves biochemical and pathological parameters of experimental chronic kidney disease

BackgroundThe growing morbidity and mortality rate of chronic kidney disease (CKD) has forced researchers to find more efficient strategies for controlling this disease. Studies have proven the important role of alteration in iron, zinc and selenium metabolism in CKD pathological process. Nanotechnology, through synthetizing nano metal-organic framework (NMOF) structures, can be employed as a valuable strategy for using these trace elements as the key for modification and improvement of CKD-related pathological events. After proving the anti-diabetic property of DIBc NMOF (which contains selenium and zinc) in the previous study, the impact of this NMOF on some important biochemical and pathological parameters of CKD was evaluated in the current study.MethodsKnowing that diabetic nephropathy (DN) is the leading cause of CKD, male wistar rats were selected and given a high fat diet for 2 weeks and then were injected with streptozotocin (35 mg/kg) to induce DN. Six weeks after streptozotocin injection, DIBc or metformin treatment started and continued for 8 weeks.ResultsEight weeks of DIBc treatment decreased plasma fasting blood glucose, blood urea nitrogen, uric acid, malondialdehyde (MDA) and HOMA-IR index compared to DN control and metformin groups. This NMOF significantly reduced urinary albumin excretion rate, MDA and 8-isoprostane, while it increased creatinine clearance in comparison to the above-mentioned groups. Renal histo-pathological images indicated that DIBc ameliorated glomerular basement membrane thickening and wrinkling, mesangial matrix expansion and hypercellularity and presence of intra-cytoplasmic hyaline droplets in proximal cortical tubules of kidney samples.ConclusionThe results showed the therapeutic effect of DIBc on important biochemical and histo-pathological parameters of CKD, so this NMOF could be regarded as a promising novel anti-CKD agent.     

Association of serum gamma-glutamyltransferase with chronic kidney disease risk: a meta-analysis

Studies on the association between gamma-glutamyltransferase (GGT) and chronic kidney disease (CKD) have produced conflicting results. This study aimed to investigate the association of elevated GGT with the risk of CKD in the adult general population by performing a meta-analysis of relevant articles. We searched PubMed, Web of Science, and Embase databases from their inception to October 2017 to identify observational studies regarding the association between serum GGT level and CKD. Pooled risk ratio (RR) and 95% confidence intervals (CI) was calculated as the effective measures. Eight studies with 116 011 individuals were included in this meta-analysis. Overall, individuals with the highest versus the lowest GGT level were not associated with an increased risk of CKD (RR 1.14; 95% CI 0.99–1.31). Subgroup analysis showed that the pooled RR for the highest versus the lowest GGT category was 1.31 (95% CI 1.06–1.60) for the Asian countries and 1.04 (95% CI 0.88–1.23) for the Western countries. In the sex-stratified analysis, no significant associations of elevated GGT with risk of CKD were found for both women (RR 0.95; 95% CI 0.84–1.07) and men (RR 1.08; 95% CI 0.86–1.36). This meta-analysis demonstrates no significant association between elevated serum GGT and risk of CKD in the adult general population. However, future well-designed studies are needed to evaluate the impact of geographical region on the association.     

Relation of neuropeptide Y gene expression and genotyping with hypertension in chronic kidney disease

ObjectivesThe prognosis of high-risk patients might be greatly ameliorated using genetic predisposition risk factors. Sympathetic activity and innate immunity related to neuropeptide Y function may be related to dyslipidemia and atherosclerosis. The aim of this study is to detect the correlation between Neuropeptide Y (NPY) SNP rs16147 and its gene expression in chronic kidney disease with and without hypertension.MethodsThis study carried out on 150 subjects who were divided into 3 main groups group (I) 50 CKD patients with hypertension, group (II) 50 CKD patients without hypertension and group (III) 50 healthy individuals. Carotid intima media thickness (CIMT) was measured by Ultrasound. Kidney function test and lipid profile were performed. Genotyping and gene expression of neuropeptide Y (NPY) were performed using real time PCR.ResultsThere was a significant increase in number and percentage of CC genotype and C allele of NPY SNP distribution in CKD patients with and without hypertension when compared to controls. A significant association was found between CC genotype and C allele and the risk of CKD with hypertension with odd ratio 3.26 and 1.77, respectively. There is a significant positive correlation between NPY gene expression level and CIMT among chronic kidney disease patients with highest level of TC, LDLc and CIMT among CC genotype of NPY gene.ConclusionA significant association was found between CC genotype and C allele of NPY at rs16147 with increase NPY gene expression and risk of developing hypertension in CKD.     

Cardiac calcium dysregulation in mice with chronic kidney disease

Cardiovascular complications are leading causes of morbidity and mortality in patients with chronic kidney disease (CKD). CKD significantly affects cardiac calcium (Ca²⁺) regulation, but the underlying mechanisms are not clear. The present study investigated the modulation of Ca²⁺ homeostasis in CKD mice. Echocardiography revealed impaired fractional shortening (FS) and stroke volume (SV) in CKD mice. Electrocardiography showed that CKD mice exhibited longer QT interval, corrected QT (QTc) prolongation, faster spontaneous activities, shorter action potential duration (APD) and increased ventricle arrhythmogenesis, and ranolazine (10 µmol/L) blocked these effects. Conventional microelectrodes and the Fluo-3 fluorometric ratio techniques indicated that CKD ventricular cardiomyocytes exhibited higher Ca²⁺ decay time, Ca²⁺ sparks, and Ca²⁺ leakage but lower [Ca²⁺]_i transients and sarcoplasmic reticulum Ca²⁺ contents. The CaMKII inhibitor KN93 and ranolazine (RAN; late sodium current inhibitor) reversed the deterioration in Ca²⁺ handling. Western blots revealed that CKD ventricles exhibited higher phosphorylated RyR2 and CaMKII and reduced phosphorylated SERCA2 and SERCA2 and the ratio of PLB-Thr17 to PLB. In conclusions, the modulation of CaMKII, PLB and late Na⁺ current in CKD significantly altered cardiac Ca²⁺ regulation and electrophysiological characteristics. These findings may apply on future clinical therapies.     

慢性肾炎大鼠的肠道菌群变化

目的 探究阳离子化牛血清白蛋白（C-BSA）慢性肾炎大鼠肠道菌群结构变化并对其代谢功能进行预测。方法 20只SD大鼠分为正常组和模型组各10只,模型组参照Border造模方法尾静脉注射C-BSA造模,6周后测定24 h尿蛋白、血清肌酐和尿素氮水平。取大鼠结肠和肾脏观察病理切片。收集大鼠粪样运用MiSeq平台进行16S rRNA测序。结果 正常组与模型组大鼠24 h尿蛋白含量、血清肌酐和尿素氮差异均存在统计学意义（均P<0.01）,模型组大鼠肾小球增大,毛细血管变窄,肠上皮损伤,发生炎性浸润。模型组大鼠普氏菌属、毛螺旋菌属相对丰度较高,且氨基酸代谢、维生素代谢和脂质代谢能力减弱。结论 C-BSA肾炎的发生不仅改变肠道菌群结构,而且影响机体代谢功能。     

CXCL16 in kidney and cardiovascular injury

CXC chemokine ligand 16 (CXCL16) is a CXC soluble chemokine, an adhesion molecule and a cell surface scavenger receptor. CXCL16 regulates inflammation, tissue injury and fibrosis. Parenchymal renal cells, vascular wall cells, leukocytes and platelets express and/or release CXCL16 under the regulation of inflammatory mediators. CXCL16 expression is increased in experimental and human nephropathies. Targeting CXCL16 protected from experimental glomerular injury or interstitial fibrosis. Conflicting results were reported for experimental cardiovascular injury. High circulating CXCL16 levels are associated to human kidney and cardiovascular disease and urinary CXCL16 may increase in kidney injury. In conclusion, mounting evidence suggests a role of CXCL16 in kidney and cardiovascular disease. However, a better understanding is still required before exploring CXCL16 targeting in the clinic.     

慢性肾病患者肠道菌群特征及与微炎症因子水平的相关性

目的 探究慢性肾病（CKD）患者肠道菌群特征及与微炎症因子水平的相关性。方法 选取2018年6月至2018年12月在莆田学院附属医院诊断及治疗的CKD患者25例（CKD组）和健康体检者25例（对照组）,对两组研究对象进行肠道微生物检测,同时比较两组研究对象炎症因子水平,应用Pearson模型探究患者肠道微生态特征与炎症因子水平的相关性。结果 CKD组与对照组研究对象的肠道菌群构成具有显著差异,其中对照组双歧杆菌、乳杆菌、产甲酸草酸杆菌、草酸杆菌属、草酸杆菌科和普拉梭菌相对丰度高于CKD组,CKD组克雷伯菌属、大肠埃希菌属、肠杆菌科、瘤胃菌科、毛螺菌科、梭杆菌属和拟杆菌目相对丰度高于对照组,CKD组患者的IL-6、TNF-α、CRP和LPa水平显著高于对照组（t=3.876、4.177、2.236、3.354,P=0.000、0.000、0.030、0.002）,Pearson相关性分析显示,双歧杆菌与IL-6、TNF-α水平呈明显负相关（r=‒0.272、‒0.482,P=0.009、0.002）,乳杆菌与IL-6、LPa水平呈明显负相关（r=‒0.438、‒0.384,P=0.005、0.014）,普拉梭菌与TNF-α水平呈明显负相关（r=-0.407,P=0.009）,瘤胃菌科与IL-6、CRP水平呈明显正相关（r=0.477、0.508,P=0.002、0.001）。结论 CKD患者肠道菌群与健康人群存在明显差异,其中益生菌水平与炎症因子呈负相关,瘤胃菌科与炎症因子呈明显的正相关     

Plasma apolipoprotein C-III metabolism in patients with chronic kidney disease

Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30–60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = −0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.     

Exome sequencing and metabolomic analysis of a chronic kidney disease and hearing loss patient family revealed RMND1 mutation induced sphingolipid metabolism defects

Mitochondrial disorders (MIDs) shows overlapping clinical presentations owing to the genetic and metabolic defects of mitochondria. However, specific relationship between inherited mutations in nuclear encoded mitochondrial proteins and their functional impacts in terms of metabolic defects in patients is not yet well explored. Therefore, using high throughput whole exome sequencing (WES), we screened a chronic kidney disease (CKD) and sensorineural hearing loss (SNHL) patient, and her family members to ascertain the mode of inheritance of the mutation, and healthy population controls to establish its rare frequency. The impact of mutation on biophysical characteristics of the protein was further studied by mapping it in 3D structure. Furthermore, LC-MS tandem mass spectrophotometry based untargeted metabolomic profiling was done to study the fluctuations in plasma metabolites relevant to disease causative mutations and kidney damage. We identified a very rare homozygous c.631G > A (p.Val211Met) pathogenic mutation in RMND1 gene in the proband, which is inherited in an autosomal recessive fashion. This gene is involved in the mitochondrial translational pathways and contribute in mitochondrial energy metabolism. The p.Val211Met mutation is found to disturb the structural orientation (RMSD is −2.95 Å) and stability (ΔΔG is −0.552 Kcal/mol) of the RMND1 protein. Plasma metabolomics analysis revealed the aberrant accumulation of metabolites connected to lipid and amino acid metabolism pathways. Of these metabolites, pathway networking has discovered ceramide, a metabolite of sphingolipids, which plays a role in different signaling cascades including mitochondrial membrane biosynthesis, is highly elevated in this patient. This study suggests that genetic defects in RMND1 gene alters the mitochondrial energy metabolism leading to the accumulation of ceramide, and subsequently promote dysregulated apoptosis and tissue necrosis in kidneys.     

根据“肠-肾轴”理论治疗慢性肾脏病的研究进展

有研究报道在慢性肾脏病的发生发展过程中可发现一系列肠道变化,并有学者用"肠-肾轴"理论阐述肾脏病中肠道的变化以及疾病过程中肾脏与肠道之间的联系,提示调节肠道菌群或可成为治疗慢性肾脏病的新方法。本文根据"肠-肾轴"理论,综述了在慢性肾脏病发展过程中肠道出现的变化,如肠内代谢物异常、肠道损伤以及肠道菌群失调等。以慢性肾脏病发生发展过程中肠道的异常变化为治疗切入点,总结了以大黄为主的中药在调节肠道功能、修复肠道屏障、纠正肠道代谢物异常等方面具有的显著疗效,为治疗慢性肾脏病及减少并发症等提供新的治疗思路和新方法。     

雷帕霉素对小鼠葡萄糖代谢水平的影响

目的探讨雷帕霉素对葡萄糖代谢水平影响的特点、机制。方法选择4周龄、雄性C57BL/6小鼠,高热量、高脂饮食喂养8周后为肥胖组(HF,n=18),普通饲料喂养为正常组(NC,n=18)。两组小鼠分别给予安慰剂(n=6)、腹腔注射雷帕霉素(2 mg/kg,隔日1次,n=6)、喂饮2.37%亮氨酸水(n=6),2周后分别行灌胃葡萄糖耐量试验(glucose tolerance test,GTT)、胰岛素耐受性试验(insulin tolerance test,ITT)以及胰岛组织病理学检查。结果正常组小鼠腹腔注射雷帕霉素后葡萄糖负荷30min血糖水平显著升高(与安慰剂组比P=0.038,与亮氨酸组比P=0.035)。肥胖组小鼠腹腔注射雷帕霉素后空腹血糖水平显著高于安慰剂组(P=0.031),葡萄糖负荷30 min血糖显著高于安慰剂组(P=0.013)、亮氨酸组(P=0.041)。仅正常组小鼠胰岛素敏感性与安慰剂组相比显著降低(P=0.039)。雷帕霉素干预后腹腔脂肪量显著减少(正常组与安慰剂组比P0.001,肥胖组与安慰剂组比P=0.013)。结论雷帕霉素对哺乳动物糖代谢水平有显著影响,正常小鼠与机体胰岛素敏感性下降有关;肥胖小鼠与胰岛素分泌功能受损、胰岛素抵抗相关。     

Interleukin-20 targets renal cells and is associated with chronic kidney disease

Interleukin (IL)-10 is an anti-inflammatory factor that suppresses renal fibrosis and improves renal function in CKD rats. IL-20 belongs to the IL-10 family; therefore, we sought to determine whether IL-20 is involved in CKD. CKD patients at stage five expressed significantly higher IL-20 in serum than controls. Immunohistochemical staining demonstrated that more IL-20 protein was expressed in the kidney tubular-epithelial cells, mesangial cells, and immune cells of CKD rats with a 5/6 nephrectomy. The lung, liver, and heart tissue of CKD rats also overexpressed IL-20. Thus, we treated two tubular epithelial cells, TKPTS and M-1 cells, with IL-20 to study its effects on CKD. IL-20 treatment induced apoptosis in these cells via caspase-3 activation. Incubating IL-20 with rat interstitial fibroblasts, NRK-49F cells, upregulated TGF-β1production, one key inducer for renal fibrogenesis. Therefore, IL-20 injured renal epithelial cells and induced fibroblasts to produce TGF-β1 that hastened the progression of CKD.     

Changes of urinary phospholipids in the chronic kidney disease patients

Abstract

Objective: To evaluate whether urinary phospholipids could be regarded as biomarkers of chronic kidney disease.

Materials and methods: Thirteen healthy volunteers and 26 consecutive chronic kidney disease patients were included. Urinary phospholipids were quantified by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Results: Urinary phosphatidylcholines concentrations (PC 16:0/16:0, 16:0/22:3, 16:0/18:1 and 16:0/18:2) were significantly higher both in glomerulonephritis group (all p?<?0.001) and in tubulointerstitial injury group (all p?<?0.05) than in healthy control group. Meanwhile, sphingomyelin concentrations (SM 18:1/16:0 and 18:1/18:0) in glomerulonephritis group were significantly higher than those in healthy control group (all p?<?0.001). Urinary PCs and SMs were positively correlated with proteinuria but negatively correlated with serum albumin. Meanwhile, PCs were positively correlated with serum creatinine.

Conclusion: Our work first demonstrated that urinary phospholipids might be biomarkers for the chronic kidney disease patients. Increased urinary phospholipids in chronic kidney disease patients might result from proteinuria, damaged kidney function or proteinuria induced hypoalbuminemia or lipotoxicity.     

Effects of exercise and lifestyle intervention on oxidative stress in chronic kidney disease

Objectives: Determine the effects of a 12-month exercise and lifestyle intervention program on changes in plasma biomarkers of oxidative stress in pre-dialysis chronic kidney disease (CKD) patients.

Methods: A total of 136 stage 3–4 CKD patients were randomized to receive standard nephrological care with (N?=?72) or without (N?=?64) a lifestyle and exercise intervention for 12 months. Plasma total F₂-isoprostanes (IsoP), glutathione peroxidase (GPX) activity, total antioxidant capacity (TAC), anthropometric and biochemical data were collected at baseline and at 12 months.

Results: There were no significant differences between groups at baseline. There were no significant differences in changes for standard care and lifestyle intervention, respectively, in IsoP (p?=?0.88), GPX (p?=?0.87), or TAC (p?=?0.56). Patients identified as having high IsoP at baseline (>250 pg/mL) had a greater decrease in IsoP with lifestyle intervention compared to standard care; however, the difference was not statistically significant (p?=?0.06). There was no difference in the change in kidney function (eGFR) between standard care and lifestyle intervention (p?=?0.33).

Discussion: Exercise and lifestyle modification in stage 3–4 CKD did not produce changes in systemic biomarkers of oxidative stress over a 12-month period, but patients with high IsoP may benefit most from the addition of intervention to standard care.     

Generation and characterization of monoclonal antibody against Advanced Glycation End Products in chronic kidney disease

Advanced Glycation End Products (AGEs) are toxins that are involved in structural and functional alterations of several organs and tissues, resulting in various pathologies. Several types of AGEs have been described but carboxymethyllysine (CML) is the major antigenic AGE compound. In this study, three different immunogenic carrier proteins (KLH, keyhole limpet hemocyanin; BSA, bovine serum albumin; and HSA, human serum albumin) were modified by glycation. The glycated molecules were used to produce epitope-specific monoclonal antibodies able to recognize the CML domain and to detect uremic toxins in the serum of patients with chronic kidney disease (CKD). A competitive ELISA was standardized in order to quantify CML in the sera of CKD patients. An increase in uremic toxins can compromise the clinical condition of these patients, thus, the detection and quantification of these toxins should contribute to a better management and understanding of this disease.     

Oxidative stress is associated with decreased heart rate variability in patients with chronic kidney disease

Objectives: Elevated oxidative stress and reduced heart rate variability (HRV) is prevalent in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality. Previous studies have identified a positive association between elevated oxidative stress and autonomic dysfunction, however this relationship has not yet been investigated in the CKD population.

Methods: Plasma was collected from 78 patients with stage 3–4 CKD (estimated glomerular filtration rate 25–60?ml/min/1.73?m²) for the assessment of oxidative stress, including plasma total F2-isoprostanes, glutathione peroxidase activity and total antioxidant capacity. Time and frequency HRV parameters were measured from a three lead electrocardiogram.

Results: Participants with elevated F2-isoprostanes had reduced HRV compared to patients with normal levels of F2-isoprostanes. A number of HRV parameters were found to be inversely correlated with F2-isoprostanes in all CKD patients, including SDNN (r?=??0.337; P?r?=??0.281, P?=?0.01), LF (r?=??0.315, P?r?=??0.288, P?=?0.01). Multiple linear regression found F2-isoprostanes to be an independent predictor of SDNN (r²?=?0.287, β?=??0.272, P?=?0.01).

Discussion: Oxidative stress is significantly and independently associated with HRV in patients with CKD. Identifying oxidative stress in the pathogenesis of autonomic dysfunction may help target therapeutic strategies.